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Evaluation of the novel USPIO GEH121333 for MR imaging of cancer immune responses. Contrast media & molecular imaging Shi, Q., Pisani, L. J., Lee, Y. K., Messing, S., Ansari, C., Bhaumik, S., Lowery, L., Lee, B. D., Meyer, D. E., Daldrup-Link, H. E. 2013; 8 (3): 281-288

Abstract

Tumor-associated macrophages (TAM) maintain a chronic inflammation in cancers, which is associated with tumor aggressiveness and poor prognosis. The purpose of this study was to: (1) evaluate the pharmacokinetics and tolerability of the novel ultrasmall superparamagnetic iron oxide nanoparticle (USPIO) compound GEH121333; (2) assess whether GEH121333 can serve as a MR imaging biomarker for TAM; and (3) compare tumor MR enhancement profiles between GEH121333 and ferumoxytol. Blood half-lives of GEH121333 and ferumoxytol were measured by relaxometry (n?=?4 each). Tolerance was assessed in healthy rats injected with high dose GEH121333, vehicle or saline (n?=?4 each). Animals were monitored for 7?days regarding body weight, complete blood counts and serum chemistry, followed by histological evaluation of visceral organs. MR imaging was performed on mice harboring MMTV-PyMT-derived breast adenocarcinomas using a 7?T scanner before and up to 72?h post-injection (p.i.) of GEH121333 (n?=?10) or ferumoxytol (n?=?9). Tumor R1 , R2 * relaxation rates were compared between different experimental groups and time points, using a linear mixed effects model with a random effect for each animal. MR data were correlated with histopathology. GEH121333 showed a longer circulation half-life than ferumoxytol. Intravenous GEH121333 did not produce significant adverse effects in rats. All tumors demonstrated significant enhancement on T1 , T2 and T2 *-weighted images at 1, 24, 48 and 72?h p.i. GEH121333 generated stronger tumor T2 * enhancement than ferumoxytol. Histological analysis verified intracellular compartmentalization of GEH121333 by TAM at 24, 48 and 72?h p.i. MR imaging with GEH121333 nanoparticles represents a novel biomarker for TAM assessment. This new USPIO MR contrast agent provides a longer blood half-life and better TAM enhancement compared with the iron supplement ferumoxytol. Copyright © 2013 John Wiley & Sons, Ltd.

View details for DOI 10.1002/cmmi.1526

View details for PubMedID 23606432

View details for PubMedCentralID PMC3662997